title: Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma.
abstract: Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas that often arises in ovarian endometriosis. We previously reported that a unique carcinogenic environment, especially iron-induced oxidative stress in endometriotic cysts may promote development of OCCC. We also identified a gene expression profile characteristic of OCCC (the "OCCC signature"). This 320-gene OCCC signature is enriched in genes associated with stress response and sugar metabolism. However, the biological implication of this profile is unclear. In this study, we have focused on the biological role of the HNF-1β gene within the OCCC signature, which was previously shown to be overexpressed in OCCC. Suppression of HNF-1β in the HNF-1β-overexpressing human ovarian cancer cell line RMG2 using short hairpin RNA resulted in a significant increase in proliferation. It also facilitated glucose uptake, glycolytic activity, and lactate secretion along with increased expression of the glucose transporter-1 (GLUT-1) gene and several key enzymes in the glycolytic process. Conversely, forced expression of HNF-1β in the serous ovarian cancer cell line, Hey, resulted in slowed cellular growth and repressed glycolytic activity. These data suggest that HNF-1β represses cell growth, and at the same time, it promotes aerobic glycolysis which is known as the "Warburg effect." As the Warburg effect is regarded as a characteristic metabolic process in cancer which may contribute to cell survival under hypoxic conditions or in a stressful environment, overexpression of HNF-1β may play an inevitable role in the occurrence of OCCC in stressful environment.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Takako
authors.initials: T
authors.lastname: Okamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondoh
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Amano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Abiko
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kosaka
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mori
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051272:Glucose Transporter Type 1; C496495:HNF1B protein, human; C495677:SLC2A1 protein, human; D051539:Hepatocyte Nuclear Factor 1-beta; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005947:Glucose
keywords: HNF1β; glucose metabolism; ovarian clear cell carcinoma